Periodic Reporting for period 3 - LUMINOUS (Studying, Measuring and Altering Consciousness through information theory in the electrical brain) Reporting period: 2018-03-01 to 2020-02-29 Summary of the context and overall objectives of the project What is consciousness? Can it be measured? While humankind has struggled with these questions for millennia, our project has focused on more modest but nonetheless ambitious and related goals. Inspired by recent developments in neuroscience and the potential role of fundamental mathematical concepts, we have studied, modelled, quantified, and attempted to alter observable aspects of consciousness. Our vision is that consciousness will someday be electromagnetically measured and altered, and that the associated needed insights will prove crucial to the development cognitive sciences. Project results have demonstrated the central role that complexity plays on consciousness. Complexity characterizes consciousness as the equilibrium between integration and information. We realized that the wakefulness dimension of consciousness is related to the thalamo-cortical connectivity, whereas the awareness dimension corresponds to different degrees of cortico-cortical connectivity. Experimental work has clearly shown that consciousness state categories are not static ones, but that the consciousness states fluctuate depending on the wakefulness degree. Thalamo-cortical connectivity appears to act as “consciousness switch”.The Luminous project has achieved different milestones in the field of neurophysiology and neurostimulation using non-invasive techniques especially relevant for sleep and disorders of consciousness, which pave new research paths for the treatment of related diseases. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far 1. The scientific framework developed along the Luminous project is based on ideas of information theory and complexity. Crucially, it also provides a bridging principle that can extent both horizontally, linking different theories of consciousness, and vertically, linking multiple scales from global EEG dynamics to the microscale level of neuronal events.2. From the technological point of view, we have deployed a closed-loop experimental prototype, in which a brain stimulation protocol is launched automatically and in real time according to an EEG feature that is being calculated online. We have used this prototype in a pilot study with MCS patients and obtained some promising initial results that show that stimulating MCS patients when they are in high vigilance levels may help improve signs of consciousness. 3. We have explored and validated a set of measures of consciousness that are conceptually related, complementary, and clinically useful. Among them the most promising ones are related with the complexity of spontaneous EEG signals. We have have successfully classified 150 conscious from unconscious subjects with 95% precision.4. We have observed an increase in the level of consciousness in 6 out of 17 MCS patients after a single session of frontoparietal tDCS network stimulation. Although the gained signs of consciousness were not sustained, this can be further explored with repeated tDCS sessions, since multisession tDCS is known to result in more long-term improvements. 5. We have experimentally shown that foetuses are able to identify and distinguish complex sound sequences and that there is a learning process involved in foetuses very similar to the one in babies, children and adults. 6. We have created a prototype to measure consciousness decrease during anaesthesia that will allow a more controlled dosage of the anaesthetic drug to avoid pain or cognitive impairments resulting from anaesthetic mis-dosing side effects. 7. For the first time we have developed and successfully used with humans an experimental system to generate and sustain specific brain oscillations using a combination of tACS and rTMS. Such a system will find applications for memory enhancement as well as treatment of sleep disorders in the short-term. 8. Project results have been disseminated among the scientific community in form of over 50 journal papers, with over one hundred conference communications. Luminous work appeared in 30 media reports, which intended to disseminate advances among the general public. Approximately 50 public events were organized by consortium members. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Project work confirmed that outcomes will have a fundamental impact in neuroscience, providing key insights into consciousness, how to model, measure and alter it. Concretely:¥ The interaction between theory, modelling, and experimental teams is showing extremely fruitful in defining physiology-based information-theory models of consciousness. The results can be verified through the relevant publications, among which is is worth pointing out the publication of “An algorithmic information theory of consciousness” and “Are there Islands of Awareness” papers. ¥ Important technological advances have been achieved by the development of 1) a computational brain model to be extensively used in consciousness studies in the future and 2) a closed-loop prototype for transcranial Electrical Stimulation. Successfully technology transfer to the clinical domain has been achieved by deploying the closed-loop system for University of Liege to conduct a study in which 12 patients are expected to be treated. ¥ We have implemented different machine learning solutions to provide Decision Support Systems in consciousness studies. A DSSs for the prediction of the outcome of tDCS treatment on DOC has been developed together with diverse diagnosis DSSs for DOCs. We believe that the DSS for tDCS outcome prediction will become an important tool not only for tDCS DOC treatments, but beyond in clinical trials of drug-based treatments to further stratify the population to be treated and therefore optimize treatment time and cost. ¥ Starlab has recently acquired a service to support a clinical trial related to the effects of the psychoactive substance in cannabis. Here it has been of paramount importance the technology advancement in Luminous, concretely in measurements of complexity based on LZW, which has been requested to be incorporated as endpoint in the study by our client. ¥ Clinical impact is based on experimental advances with respect to the SoA. This have been most clearly achieved on the outstanding clinical applications to: 1) alter oscillatory brain activity in sleep through a combination of different types of Non-Invasive Brain Stimulation, 2) provide a more accurate diagnosis of Disorders of Consciousness (DOC) through numerous novel metrics, 3) enhance consciousness levels in DOC at individual level through the electrical stimulation of the consciousness network, and 4) automatically titrate anesthetics in real-time titration. Project developed techniques open as well a new window into the study of brain and consciousness in utero. ¥ One important part of the impact was the engagement of the general public in discussions on project goals and achievements. In this context three events for the general public have been organized: Oxford Public Café, Liege Coma Day, and the Future Tech Week event at Starlab. Moreover, a survey has been conducted on the usage of NIBS for DOC treatment involving the general public.Although Luminous has not provided an answer for the fundamental question of what consciousness is, or definitive technologies to measure and control it, we believe it has made important contributions to the field from many angles. We are convinced that it will provide a firmer foothold for future research programs with our shared vision and mission. Different consciousness states and its characterization (Laureys 2005) Probing the brain with NIBS (Casali et al 2013) TMS+EGG apparatus used for measuring consciousness Project logo Technologies for consciousness studies in Luminous fMEG study for the exploration of foetal consciousness Luminous last plenary meeting at the University of Oxford
